Mapping human tissues with highly multiplexed RNA in situ hybridization
Abstract In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46437-y |
| _version_ | 1797247171781722112 |
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| author | Kian Kalhor Chien-Ju Chen Ho Suk Lee Matthew Cai Mahsa Nafisi Richard Que Carter R. Palmer Yixu Yuan Yida Zhang Xuwen Li Jinghui Song Amanda Knoten Blue B. Lake Joseph P. Gaut C. Dirk Keene Ed Lein Peter V. Kharchenko Jerold Chun Sanjay Jain Jian-Bing Fan Kun Zhang |
| author_facet | Kian Kalhor Chien-Ju Chen Ho Suk Lee Matthew Cai Mahsa Nafisi Richard Que Carter R. Palmer Yixu Yuan Yida Zhang Xuwen Li Jinghui Song Amanda Knoten Blue B. Lake Joseph P. Gaut C. Dirk Keene Ed Lein Peter V. Kharchenko Jerold Chun Sanjay Jain Jian-Bing Fan Kun Zhang |
| author_sort | Kian Kalhor |
| collection | DOAJ |
| description | Abstract In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts. |
| first_indexed | 2024-04-24T19:54:27Z |
| format | Article |
| id | doaj.art-f8cae104acb14c0f8f561559231a314f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T19:54:27Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f8cae104acb14c0f8f561559231a314f2024-03-24T12:25:50ZengNature PortfolioNature Communications2041-17232024-03-0115111710.1038/s41467-024-46437-yMapping human tissues with highly multiplexed RNA in situ hybridizationKian Kalhor0Chien-Ju Chen1Ho Suk Lee2Matthew Cai3Mahsa Nafisi4Richard Que5Carter R. Palmer6Yixu Yuan7Yida Zhang8Xuwen Li9Jinghui Song10Amanda Knoten11Blue B. Lake12Joseph P. Gaut13C. Dirk Keene14Ed Lein15Peter V. Kharchenko16Jerold Chun17Sanjay Jain18Jian-Bing Fan19Kun Zhang20Department of Bioengineering, University of California San DiegoDepartment of Bioengineering, University of California San DiegoDepartment of Bioengineering, University of California San DiegoDepartment of Bioengineering, University of California San DiegoDepartment of Bioengineering, University of California San DiegoDepartment of Bioengineering, University of California San DiegoSanford Burnham Prebys Medical Discovery InstituteDepartment of Bioengineering, University of California San DiegoDepartment of Biomedical Informatics, Harvard Medical SchoolAltos LabsDepartment of Bioengineering, University of California San DiegoDepartment of Medicine, Washington University School of MedicineDepartment of Bioengineering, University of California San DiegoDepartment of Pathology and Immunology, Washington University School of MedicineDepartment of Laboratory Medicine and Pathology, University of Washington School of MedicineAllen Institute for Brain ScienceDepartment of Biomedical Informatics, Harvard Medical SchoolSanford Burnham Prebys Medical Discovery InstituteDepartment of Medicine, Washington University School of MedicineIlluminaDepartment of Bioengineering, University of California San DiegoAbstract In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.https://doi.org/10.1038/s41467-024-46437-y |
| spellingShingle | Kian Kalhor Chien-Ju Chen Ho Suk Lee Matthew Cai Mahsa Nafisi Richard Que Carter R. Palmer Yixu Yuan Yida Zhang Xuwen Li Jinghui Song Amanda Knoten Blue B. Lake Joseph P. Gaut C. Dirk Keene Ed Lein Peter V. Kharchenko Jerold Chun Sanjay Jain Jian-Bing Fan Kun Zhang Mapping human tissues with highly multiplexed RNA in situ hybridization Nature Communications |
| title | Mapping human tissues with highly multiplexed RNA in situ hybridization |
| title_full | Mapping human tissues with highly multiplexed RNA in situ hybridization |
| title_fullStr | Mapping human tissues with highly multiplexed RNA in situ hybridization |
| title_full_unstemmed | Mapping human tissues with highly multiplexed RNA in situ hybridization |
| title_short | Mapping human tissues with highly multiplexed RNA in situ hybridization |
| title_sort | mapping human tissues with highly multiplexed rna in situ hybridization |
| url | https://doi.org/10.1038/s41467-024-46437-y |
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